Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Effective therapies for metastatic osteosarcoma (OS) remain a major clinical unmet need. Targeting mRNA translation in metastatic OS represents an attractive option, as selective translation under stress supports the rapid synthesis of cytoprotective proteins that facilitate metastatic competence. We therefore assessed eukaryotic translation factors in OS, revealing high expression of eIF4A1 in metastatic OS. The eIF4A1 inhibitor, CR-1-31B, potently inhibited metastatic OS growth in vitro and reduced lung tumor burden in orthotopic mouse models. CR-1-31B synergized with the oxidative stress inducer, tert-butylhydroquinone (tBHQ), to enhance cell death under oxidative stress. Proteomic analysis revealed a subset of proteins that were upregulated by tBHQ alone, but inhibited by co-treatment of CR-1-31B, most notably the NRF2 antioxidant transcription factor, and NRF2 inactivation phenocopied CR-1-31B in blocking OS lung metastasis in vivo. Collectively, our data reveal that targeting eIF4A1 with CR-1-31B is highly effective in blocking OS metastasis by blunting the NRF2 antioxidant response.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:Expression data from U-2 OS osteosarcoma cell lines stably expressing an S22A-progerin mutant compared with U-2 OS expressing wt-progerin
